Synthesis, Biological Evaluation, and In Silico Studies of Novel Coumarin-Based 4H,5H-pyrano[3,2-c]chromenes as Potent β-Glucuronidase and Carbonic Anhydrase Inhibitors

The search for novel heterocyclic compounds with a natural product skeleton as potent enzyme inhibitors against clinical hits is our prime concern in this study. Here, a simple and facile two-step strategy has been designed to synthesize a series of novel coumarin-based dihydropyranochromenes (12a-12m) in a basic moiety. The synthesized compounds were thus characterized through spectroscopic techniques and screened for inhibition potency against the cytosolic hCA II isoform and beta-glucuronidase. Few of these compounds were potent inhibitors of hCA II and beta-glucuronidase with varying IC50 values ranging from 4.55 +/- 0.22 to 21.77 +/- 3.32 mu M and 440.1 +/- 1.17 to 971.3 +/- 0.05 mu M, respectively. Among the stream of synthesized compounds, 12e and 12i were the most potent inhibitors of beta-glucuronidase, while 12h, 12i, and 12j showed greater potency against hCA II. In silico docking studies illustrated the significance of substituted groups on the pyranochromene skeleton and binding pattern of these highly potent compounds inside enzyme pockets.

Automated summary

This study focuses on the search for novel heterocyclic compounds with a natural product skeleton as potent enzyme inhibitors. A simple and facile strategy was designed to synthesize a series of coumarin-based compounds, which were then screened and characterized for their inhibition potency. Several compounds showed strong inhibitory activity against the target enzymes, indicating their potential for drug development.